Not so useless after all: even “gene deserts” have oases

Huge "gene deserts" DNA don't code for proteins. Can they do anything? New …

As researchers sequenced the genomes of mammals, they came across large regions that didn't seem to contain any protein-coding genes. These "gene deserts" often stretched for thousands of DNA base pairs (called kilobases), and their discovery left researchers arguing about whether they served any function.

One hint that these deserts might be important was the finding that a gene desert on the short arm of chromosome 9 contains some DNA base differences (single nucleotide polymorphisms, or SNPs) associated with coronary artery disease; others were associated with type 2 diabetes.

The desert runs for almost 200 kilobases. Since there were no real genes nearby, it was unclear exactly how these desert SNPs could manifest themselves as disease. A recent study by Kelly Frazer and colleagues at UCSD, published in Nature, may provide a clue: there are 33 genetic control elements in the desert region.

These control elements are called "enhancers." They are regions of DNA to which proteins bind in a sequence-specific manner; this binding enhances the activity of genes on the same chromosome. An enhancer sequence does not need to be close to the gene it acts upon; it is brought into physical proximity with its target gene through the geometric conformation of the chromosome.

The SNP most consistently associated with coronary artery disease is located in a STAT-1 binding site. STAT-1 is a protein that mediates the inflammatory response and is associated with angiogenesis and atherosclerosis. When cells that have one copy of the risk-associated SNP are treated with a pro-inflammation factor called interferon-γ, STAT-1 binds to the site. However, in cell lines homozygous for the risk SNP, STAT-1 failed to bind to its site. (The risk haplotype confers a two-fold greater risk of heart attack to Caucasians who carry it.)

To determine which genes are affected by these newly found enhancers, the researchers looked at all of the genes located within 2 megabases (millions of bases) of the desert region. There are twenty genes upstream and one downstream, and researchers used a new technique to study long range genetic interactions, called chromatin conformation capture (or 3C). In 3C, interacting regions of DNA, along with any proteins bound there, are chemically linked, and then excess DNA is cut away.

3C showed that the enhancers interacted with four nearby genes, and researchers confirmed these interactions with more traditional techniques. Interestingly, the association between the enhancers and the three genes implicated in coronary artery disease was modulated by interferon-γ.

This study thus validated a relatively new technique, 3C; defined a link between genetic susceptibility to heart disease and inflammation; and demonstrated how genome wide association studies can be used to find novel genetic elements with clinical importance.

Researches still don't get that nothing in biological systems is there "for no use".

No respected researchers assume these vast areas of 'junk' DNA does nothing. Its just very difficult to find out what they do if they are not protein coding sequences or part of a promoter region of a gene.

Researches still don't get that nothing in biological systems is there "for no use".

I'll steal the following quote:"The onion test is a simple reality check for anyone who thinks they have come up with a universal function for non-coding DNA. Whatever your proposed function, ask yourself this question: Can I explain why an onion needs about five times more non-coding DNA for this function than a human?"

This post clarified for me what so-called "junk DNA" really is, and why computer code is a pretty terrible analogy for a genome.

Should I spoil the ending? Eh, why not:

Quote:

...you could say they have a rough, general role: they are the plastic boxes and styrofoam packing peanuts of the functional elements of the genome. They may do something, but it's not specific, and it's not particularly dependent on the code.

Junk DNA isn't merely stuff that we don't understand. It's stuff that we know something about, and know how it fits into the ecosystem of the cell, and that we call junk because we know what it does — it mainly sits up in the attic, garage, and basement, gathering dust and taking up space.

Dr Jay wins the thread... Although my personal favourite version of the Onion test is asking someone to explain why the largest known genome belongs to an amoeboid, which happens to have 200 times as many base pairs as for a human - 200 times!

Of course this sort of discussion really needs to come with a discussion on the mechanisms that generate these ridiculously huge genomes. Gene duplication is actually a very common type of mutation and can occur in both diploid and haploid cells:http://en.wikipedia.org/wiki/Gene_duplication

The short version is that if this happens in normal (non-gamete) cells, then it can sometimes result in bad effects for the organism, such as cancer. But often it just provides a second copy of genes, which is an important result. If you have two copies of a gene, it doesn't matter (well, matters less)if one gets broken by further mutation, meaning that evolution can "play" with this second copy without too badly hurting the organism.

At any rate, there are no known limits on the doubling of genomes, which explains how we can end up with tiny organisms with ridiculously huge genomes - it's an example of The Drunk's Walk:http://en.wikipedia.org/wiki/Random_walk

Informative article. I worked for a biotech firm in 2000-2002, and we were noting SNP locations. But the reasons for the massive amounts of "junk DNA" between the genes was a mystery at that time. Good to hear there's an explanation after all. (Note that some other species of animals and plants have very "compact" DNA with very little "junk" between the active genetic sequences. -- eg: pufferfish)

I'm sure we'll eventually discover more useful tidbits in the desert. Keep up the good work.

Anyone who is asking why an onion needs its large genome is misunderstanding evolutionary biology. There is no optimality criterion in evolution. Evolution is about what is possible, what is good enough, what is better and what is worse. An onion's large genome is obviously good enough. If there was a way for the onion to have a smaller genome and that smaller genome was better, then we are likely to see onions with smaller genomes, if not now, in the future. Similarly, if there were onions with even larger genomes that weren't worse, then we are likely to see onions with large genomes.

Onion World isn't reporting on an onion crisis because onions have large genomes.

Anyone who is asking why an onion needs its large genome is misunderstanding evolutionary biology. There is no optimality criterion in evolution. Evolution is about what is possible, what is good enough, what is better and what is worse. An onion's large genome is obviously good enough. If there was a way for the onion to have a smaller genome and that smaller genome was better, then we are likely to see onions with smaller genomes, if not now, in the future.

Anyone who is asking why an onion needs its large genome is misunderstanding evolutionary biology. There is no optimality criterion in evolution. Evolution is about what is possible, what is good enough, what is better and what is worse. An onion's large genome is obviously good enough.

AFAICT that's the whole point of the exercise. Everything you wrote applies to humans too. Our genomes been shaped over time by the same general processes (different in the details of course) that make onions what they are. Our genes aren't special and purposeful (aside from our own sloppy, localized artificial selection).

This is more true than you may have intended; organisms form symbiotic relationships in a variety of ways. Hitching yourself to the human wagon is a pretty damn good way to ensure the survival and spread of your genes (from the point of view of species like onions, corn, wheat, dogs, cats, a variety of gut bacteria, etc).

So in fact there may be evolutionary pressure for the onion to be tasty to humans. (Our long history of genetic engineering notwithstanding)

Researches still don't get that nothing in biological systems is there "for no use".

This is unfair. You have to distinguish between scientists and the authors of popular books (including, unfortunately, scientists acting as authors of popular books). When scientists are acting as scientists (and when they are writing papers, talking with colleagues, etc) they are cautious about what is and is not definitely known. But you can't write something for the public that has a disclaimer attached to every sentence. So we have an unfortunate situation where the public understanding, even of the well-informed public, lags maybe ten years behind what scientists themselves know.

If biologists were really as foolish as you say, then a result like this would never even have been found. Sequencing the genome would have consisted of picking out the protein-coding parts (ESTs and all that), and no-one would be sequencing the relevant "desert" in the genome. Of course the original late 90's genome project concentrated on protein coding regions because that was easiest to tackle at the time, and was felt (perhaps rightly, perhaps wrongly) to be the easiest to immediately interpret for medical significance. But work did not stop there, and we are seeing ever more investigation of features that do not fit into that simple-minded paradigm, whether it's investigation of the regulatory areas (as opposed to protein coding areas) or investigation of copy NUMBER polymorphism (as opposed to simply investigating the difference between "the" (assumed single) copy of a gene in two different individuals, or investigation of the various ways in which RNA acts beyond the simple 60s standard dogma.

But the reasons for the massive amounts of "junk DNA" between the genes was a mystery at that time. Good to hear there's an explanation after all.

It is important to understand that the words "reason" and "explanation" have multiple meanings.

In the blog post by pharyngula quoted above, pharyngula has a particular point in mind --- he is trying to deal with the ongoing idiocy of creationism and its ongoing twisting of the meanings of whatever its is biologists published last week. Creationists have a view of "reason" and "explanation" that, no matter what, boils down to "it's this way because god wants it to be this way", and in consequence pharyngula perhaps overstates the case.

Having said that, we've know for a long time, certainly from a lot earlier than 2000, "why" there is "junk DNA" in the genome, namely that it represents various sorts of "parasitic DNA", mutations that are able to hijack the replication machinery in such a way as to generate many copies of themselves; and there has not evolved any strong mechanism to weed these out (perhaps because there's no easy way to mutate to such a mechanism, perhaps because there's just no real selection pressure to have such a mechanism).Having said that --- we have this random stuff because it is parasitical --- there remains the possibility that there are cases (perhaps few, perhaps many) where this stuff has in turn been hijacked to perform some useful role. And this is where pharyngula's confident assertions are perhaps less than helpful. Boldly asserting that this stuff is always useless, when we don't actually know that for a fact, makes one look silly (and allows the creationists some temporary victory) when a result like this turns up.

But the reasons for the massive amounts of "junk DNA" between the genes was a mystery at that time. Good to hear there's an explanation after all.

It is important to understand that the words "reason" and "explanation" have multiple meanings.

In the blog post by pharyngula quoted above, pharyngula has a particular point in mind --- he is trying to deal with the ongoing idiocy of creationism and its ongoing twisting of the meanings of whatever its is biologists published last week. Creationists have a view of "reason" and "explanation" that, no matter what, boils down to "it's this way because god wants it to be this way", and in consequence pharyngula perhaps overstates the case.

Having said that, we've know for a long time, certainly from a lot earlier than 2000, "why" there is "junk DNA" in the genome, namely that it represents various sorts of "parasitic DNA", mutations that are able to hijack the replication machinery in such a way as to generate many copies of themselves; and there has not evolved any strong mechanism to weed these out (perhaps because there's no easy way to mutate to such a mechanism, perhaps because there's just no real selection pressure to have such a mechanism).Having said that --- we have this random stuff because it is parasitical --- there remains the possibility that there are cases (perhaps few, perhaps many) where this stuff has in turn been hijacked to perform some useful role. And this is where pharyngula's confident assertions are perhaps less than helpful. Boldly asserting that this stuff is always useless, when we don't actually know that for a fact, makes one look silly (and allows the creationists some temporary victory) when a result like this turns up.

But the reasons for the massive amounts of "junk DNA" between the genes was a mystery at that time. Good to hear there's an explanation after all.

It is important to understand that the words "reason" and "explanation" have multiple meanings.

In the blog post by pharyngula quoted above, pharyngula has a particular point in mind --- he is trying to deal with the ongoing idiocy of creationism and its ongoing twisting of the meanings of whatever its is biologists published last week. Creationists have a view of "reason" and "explanation" that, no matter what, boils down to "it's this way because god wants it to be this way", and in consequence pharyngula perhaps overstates the case.

Having said that, we've know for a long time, certainly from a lot earlier than 2000, "why" there is "junk DNA" in the genome, namely that it represents various sorts of "parasitic DNA", mutations that are able to hijack the replication machinery in such a way as to generate many copies of themselves; and there has not evolved any strong mechanism to weed these out (perhaps because there's no easy way to mutate to such a mechanism, perhaps because there's just no real selection pressure to have such a mechanism).Having said that --- we have this random stuff because it is parasitical --- there remains the possibility that there are cases (perhaps few, perhaps many) where this stuff has in turn been hijacked to perform some useful role. And this is where pharyngula's confident assertions are perhaps less than helpful. Boldly asserting that this stuff is always useless, when we don't actually know that for a fact, makes one look silly (and allows the creationists some temporary victory) when a result like this turns up.

But the reasons for the massive amounts of "junk DNA" between the genes was a mystery at that time. Good to hear there's an explanation after all.

It is important to understand that the words "reason" and "explanation" have multiple meanings.

In the blog post by pharyngula quoted above, pharyngula has a particular point in mind --- he is trying to deal with the ongoing idiocy of creationism and its ongoing twisting of the meanings of whatever its is biologists published last week. Creationists have a view of "reason" and "explanation" that, no matter what, boils down to "it's this way because god wants it to be this way", and in consequence pharyngula perhaps overstates the case.

Having said that, we've know for a long time, certainly from a lot earlier than 2000, "why" there is "junk DNA" in the genome, namely that it represents various sorts of "parasitic DNA", mutations that are able to hijack the replication machinery in such a way as to generate many copies of themselves; and there has not evolved any strong mechanism to weed these out (perhaps because there's no easy way to mutate to such a mechanism, perhaps because there's just no real selection pressure to have such a mechanism).Having said that --- we have this random stuff because it is parasitical --- there remains the possibility that there are cases (perhaps few, perhaps many) where this stuff has in turn been hijacked to perform some useful role. And this is where pharyngula's confident assertions are perhaps less than helpful. Boldly asserting that this stuff is always useless, when we don't actually know that for a fact, makes one look silly (and allows the creationists some temporary victory) when a result like this turns up.

Sorry, but WTF is with the commenting system?Every post I make throws up a 404 error, but then gets posted anyway, resulting in multiple posts.

Specifically we see the words (as I have just seen, yet again)

"four oh four

There is no content at this address. We have a lovely form you can fill out if you were expecting particular content. The form is deficient, unfortunately, in that it doesn't default to the URL you're viewing now. We would like to get this fixed, interwebs willing!"